Kilbourn R G, Cromeens D M, Chelly F D, Griffith O W
Department of Genitourinary Oncology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Crit Care Med. 1994 Nov;22(11):1835-40.
To evaluate the hemodynamic effects of the nitric oxide inhibitor, NG-methyl-L-arginine, and dobutamine during experimental endotoxemia.
Prospective, randomized, controlled animal study.
University research laboratory.
Adult, male mongrel dogs.
After catheterization with a flow-directed, thermal-dilution pulmonary artery flotation catheter and arterial catheter, awake dogs received either NG-methyl-L-arginine or dobutamine alone or in combination (controls; n = 5). Other animals were administered endotoxin (50 micrograms/kg), then received either NG-methyl-L-arginine alone or in combination with dobutamine after the onset of hypotension (endotoxin-treated; n = 5).
Both dobutamine and NG-methyl-L-arginine alone had a small, but significant vasopressor effect on control animals. In contrast, administration of the combination of NG-methyl-L-arginine and dobutamine resulted in a 48.6% increase in mean arterial pressure, an effect which was dose-dependent with respect to NG-methyl-L-arginine. In dogs treated with 50 micrograms/kg of endotoxin, hypotension could be only partially reversed by NG-methyl-L-arginine, mainly due to a decline in cardiac output. Co-infusion of dobutamine reversed this depression of cardiac output and resulted in a complete restoration of blood pressure.
Later stages of septic shock are characterized by hypotension and decreased myocardial performance. A major mediator of hypotension is nitric oxide, a vasodilatory agent derived from L-arginine. Administration of the arginine derivative, NG-methyl-L-arginine, improved systemic vascular resistance but not myocardial performance. The addition of an inotropic agent to NG-methyl-L-arginine, a nitric oxide synthase inhibitor, resulted in an enhancement of the antihypotensive action of NG-methyl-L-arginine through the restoration of cardiac output. The synergistic action between dobutamine and NG-methyl-L-arginine may be of therapeutic value in the treatment of septic shock.
评估一氧化氮抑制剂NG-甲基-L-精氨酸和多巴酚丁胺在实验性内毒素血症期间的血流动力学效应。
前瞻性、随机、对照动物研究。
大学研究实验室。
成年雄性杂种犬。
在用血流导向热稀释肺动脉漂浮导管和动脉导管进行插管后，清醒的犬只单独或联合接受NG-甲基-L-精氨酸或多巴酚丁胺治疗（对照组；n = 5）。其他动物给予内毒素（50微克/千克），然后在低血压发作后单独或联合多巴酚丁胺接受NG-甲基-L-精氨酸治疗（内毒素治疗组；n = 5）。
多巴酚丁胺和NG-甲基-L-精氨酸单独使用时对对照动物均有轻微但显著的升压作用。相比之下，联合使用NG-甲基-L-精氨酸和多巴酚丁胺可使平均动脉压升高48.6%，该效应与NG-甲基-L-精氨酸呈剂量依赖性。在用50微克/千克内毒素治疗的犬只中，NG-甲基-L-精氨酸只能部分逆转低血压，主要是由于心输出量下降。联合输注多巴酚丁胺可逆转心输出量的这种降低，并导致血压完全恢复。
感染性休克后期的特征是低血压和心肌功能下降。低血压的主要介质是一氧化氮，一种由L-精氨酸衍生的血管舒张剂。给予精氨酸衍生物NG-甲基-L-精氨酸可改善全身血管阻力，但不能改善心肌功能。在一氧化氮合酶抑制剂NG-甲基-L-精氨酸中添加一种正性肌力药物，可通过恢复心输出量增强NG-甲基-L-精氨酸的抗低血压作用。多巴酚丁胺和NG-甲基-L-精氨酸之间的协同作用在感染性休克的治疗中可能具有治疗价值。
